Use Of Tape Strips To Detect Immune And Barrier Abnormalities In The Skin Of Children With Early-Onset Atopic Dermatitis

JAMA DERMATOLOGY(2020)

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摘要
Question Can tape strips serve as a minimally invasive approach to assess biomarkers for early-onset pediatric atopic dermatitis? Findings In this cross-sectional study of 51 children younger than 5 years with and without atopic dermatitis, the use of tape strips, a minimally invasive approach for skin sampling, detected the cutaneous immune and barrier abnormalities of early-onset atopic dermatitis in infants and young children and defined biomarkers that are associated with disease severity, pruritus, and transepidermal water loss. Meaning Minimally invasive tape strips can be used to broadly characterize immune and epidermal barrier biomarkers of the lesional and nonlesional skin of children with early-onset pediatric atopic dermatitis, providing a useful, noninvasive approach for pediatric clinical trials and longitudinal studies. Importance Molecular profiling of skin biopsies is the criterion standard for evaluating the cutaneous atopic dermatitis (AD) phenotype. However, skin biopsies are not always feasible in children. A reproducible minimally invasive approach that can track cutaneous disease in pediatric longitudinal studies or clinical trials is lacking. Objective To assess a minimally invasive approach using tape strips to identify skin biomarkers that may serve as a surrogate to biomarkers identified using whole-tissue biopsies. Design, Setting, and Participants This cross-sectional study of 51 children younger than 5 years recruited children with moderate to severe AD and children without AD from the dermatology outpatient clinics at a children's hospital. Sixteen tape strips were serially collected from the nonlesional and lesional skin of 21 children who had AD and were less than 6 months from disease initiation and from the normal skin of 30 children who did not have AD between January 22, 2016, and April 20, 2018. Main Outcomes and Measures Gene and protein expression were evaluated using quantitative real-time polymerase chain reaction and immunohistochemistry. Results A total of 51 children younger than 5 years were included in the study; 21 children had moderate to severe AD with less than 6 months of disease duration, and 30 children did not have AD. Of the 21 children with AD, the mean (SD) age was 1.7 (1.7) years, and most were male (15 [71.4%] and white (15 [71.4%]). Of the 30 children without AD, the mean (SD) age was 1.8 (2.0) years, and most were female (20 [66.7%]) and white (22 [73.3%]). Seventy-seven of 79 evaluated immune and barrier gene products were detected (gene detection rate, 97%) in 70 of 71 tape strips (sample detection rate, 99%), with 53 of 79 markers differentiating between children with lesional and/or nonlesional AD from children without AD. Many cellular markers of T cells (CD3), AD-related dendritic cells (Fc epsilon RI and OX40 ligand receptors), and key inflammatory (matrix metallopeptidase 12), innate (interleukin 8 [IL-8] and IL-6), helper T cell 2 (T(H)2; IL-4, IL-13, and chemokines CCL17 and CCL26), and T(H)17/T(H)22 (IL-19, IL-36G, and S100A proteins) genes were significantly increased in lesional and nonlesional AD compared with tape strips from normal skin. For example, IL-4 mean (SE) for lesional was -15.2 (0.91) and normal was -19.5 (0.48); P < .001. Parallel decreases occurred in epidermal barrier gene products (FLG, CLDN23, and FA2H) and negative immune regulators (IL-34 and IL-37). For example, the decrease for FLG lesional was mean (SE) -2.9 (0.42) and for normal was 2.2 (0.45); P < .001. Associations were found between disease severity or transepidermal water loss and T(H)2 (IL-33 and IL-4R) and T(H)17/T(H)22 (IL-36G and S100As) products in lesional and nonlesional AD skin (evaluated using the SCORing Atopic Dermatitis, Eczema Area and Severity Index, and Pruritus Atopic Dermatitis Quickscore tools). Conclusions and Relevance In this study, tape strips provide a minimally invasive alternative for serially evaluating AD-associated cutaneous biomarkers and may prove useful for tracking pediatric AD therapeutic response and predicting future course and comorbidities. This cross-sectional study examines whether tape strips might be used to detect immune and barrier abnormalities and to define biomarkers associated with atopic dermatitis in children younger than 5 years with early-onset atopic dermatitis.
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